Department of Medical Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea; Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, Republic of Korea; BK21Plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan, Republic of Korea.
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
J Clin Lipidol. 2017 Nov-Dec;11(6):1318-1328.e3. doi: 10.1016/j.jacl.2017.08.020. Epub 2017 Sep 14.
Fetal growth restriction (GR) is associated with perinatal mortality and subsequent metabolic disorders in adulthood. Until now, there is little information regarding changes in the properties of lipoproteins from growth-restricted fetuses and their maternal sera.
To identify unique lipoprotein biomarkers for fetal GR in maternal and cord sera from small neonates, we analyzed lipoprotein compositions and functions.
Lipoprotein compositions and functions were compared between cord blood and maternal blood among small for gestational age neonates (SGA; n = 15, 2589 ± 50 g) and appropriate for gestational age neonates (AGA; n = 15) in Korea.
Cord blood from the SGA group showed 2-fold higher triglyceride (TG) and TG/high-density lipoprotein cholesterol levels than the AGA group as well as significantly lower (up to 20%) paraoxonase activity and apolipoprotein (apo) A-I content. The SGA group showed the highest cholesteryl ester transfer protein activities in both cord and maternal sera. SGA neonates showed elevated apo-B content in very low-density lipoprotein, 52% reduction of apo A-I content in high-density lipoprotein, and 30% increased glycation (P < .001) compared with AGA neonates. Especially, low-density lipoprotein from the SGA group showed 1.9-fold higher sensitivity to oxidation as well as 3-fold greater uptake into macrophages, suggesting stronger proatherosclerotic properties. Lipoproteins from maternal serum of SGA neonates showed greater oxidation along with TG enrichment and loss of antioxidant ability. On microinjection of cord serum (50 nL) into zebrafish embryos, the SGA group showed the most severe embryonic damage.
Lipoproteins from cord and maternal sera of SGA neonates resulted in severe impairment of functional and structural correlations accompanied by greater pro-oxidant and proatherosclerotic properties.
胎儿生长受限(GR)与围产期死亡率和随后的成年期代谢紊乱有关。到目前为止,关于生长受限胎儿及其母体血清中脂蛋白性质的变化知之甚少。
为了鉴定小胎龄儿母血清和脐血清中胎儿生长受限的独特脂蛋白生物标志物,我们分析了脂蛋白的组成和功能。
比较了韩国小胎龄儿(SGA;n=15,2589±50g)和适于胎龄儿(AGA;n=15)的脐血和母血中的脂蛋白组成和功能。
SGA 组的脐血中甘油三酯(TG)和 TG/高密度脂蛋白胆固醇水平比 AGA 组高 2 倍,而过氧化物酶和载脂蛋白(apo)A-I 含量低(低至 20%)。SGA 组在脐血和母血中均表现出最高的胆固醇酯转移蛋白活性。SGA 新生儿极低密度脂蛋白中的载脂蛋白 B 含量升高,高密度脂蛋白中的载脂蛋白 A-I 含量降低 52%,糖化增加 30%(P<.001),与 AGA 新生儿相比。特别是,SGA 组的低密度脂蛋白对氧化的敏感性增加了 1.9 倍,被巨噬细胞摄取的能力增加了 3 倍,提示其具有更强的动脉粥样硬化形成特性。SGA 新生儿的母血清脂蛋白表现出更大的氧化作用,伴随着 TG 富集和抗氧化能力丧失。当将脐血清(50nL)注入斑马鱼胚胎时,SGA 组表现出最严重的胚胎损伤。
SGA 新生儿的脐血和母血清中的脂蛋白导致功能和结构相关性严重受损,同时具有更强的促氧化剂和动脉粥样硬化形成特性。